Sarecycline: A Narrow-Spectrum Antibiotic

Susuana Adjei, MD; Austinn C. Miller, MD; Laurie A. Temiz, BA; Stephen K. Tyring, MD, PhD, MBA


Skin Therapy Letter. 2022;27(3):5-7. 

In This Article

Abstract and Introduction


Tetracycline-class drugs have been used for first-line treatment of moderate-to-severe acne and rosacea for decades. Recently, a new third generation tetracycline, sarecycline, was US FDA-approved for the treatment of moderate-to-severe acne. This narrow-spectrum tetracycline-derived antibiotic has been shown to be effective with an improved safety profile.


To date, one of the first-line classes of oral antibiotic treatments for moderate-to-severe acne has been tetracycline-class antibiotics due to their anti-inflammatory effects, antimicrobial activity, bioavailability, and lipophilicity.[1] The pathogenesis of acne vulgaris is multifaceted with key factors being abnormal follicular keratinization, Cutibacterium acnes (C. acnes) proliferation/colonization, and increased sebum production.[2] Inflammation also ensues with the expression and upregulation of inflammatory factors/cells such as CD3+, CD4+ T cells, interleukin-1, integrins, toll-like receptors, and macrophages.[2]

Various methods for grading acne severity have been debated. Consensus remains elusive, as acne assessment must account for a spectrum of factors such as the number, location, type of lesions, associated scarring, and psychosocial influences.[1,3] In fact, the established scoring tools Global Acne Grading System (GAGS) and Investigator Global Assessment (IGA), which are widely used in clinical trials, FDA efficacy endpoints, and patient care, do not account for all the associated factors in acne assessment.[3]

Moderate-to-severe acne classically presents with inflamed papules, pustules, and occasional nodules with lesions commonly affecting the face, chest, and back.[4,5] Oral antibiotics are a mainstay of treatment (Table 1).[1] Tetracyclines, specifically doxycycline and minocycline, are broad-spectrum antibiotics widely used for acne treatment as they limit inflammation by inhibition of protein synthesis and proliferation of C. acnes.[6] However, because of their broad-spectrum activity, tetracyclines not only contribute to the emergence of bacterial resistance, but also disrupt the gut and skin normal microflora, resulting in dysbiosis.[7,8] Dysbiosis of the gut has been linked to inflammatory bowel disease. Doxycycline has shown to be associated with 2.25-fold increase in the risk of developing Crohn's disease.[9]

In 2018, a new tetracycline derivative, sarecycline, was US FDA-approved for the treatment of inflammatory lesions of non-nodular, moderate-to-severe acne vulgaris in patients aged 9 years and older.[10] This once-daily 1.5 mg/kg antibiotic exhibits a better tolerability and efficacy profile as a result of its narrow-spectrum coverage against C. acnes and clinically-relevant gram-positive bacteria with little activity against gram-negative bacteria commonly found in the human gut.[10] In vitro studies by Zhanel et al. showed that all tetracyclines had similar activity against C. acnes, even isolates highly resistant against erythromycin ranging at minimum inhibitory concentration (MIC) of 0.5 µg/mL to 32 µg/mL.[6] Activity against methicillin-susceptible and resistant isolates of Staphylococcus aureus (including MRSA) revealed a MIC90 of all tetracyclines, including sarecycline, to be 0.5 µg/mL.[6] Compared to doxycycline and minocycline, sarecycline had little or no activity against gram-negative enteric bacilli with MIC50 at 32 µg/mL (16-fold less than doxycycline and minocycline).[6]